GENE NETWORKS: FROM MOLECULES TO MECHANISTIC MODELS

基因网络：从分子到机制模型

• 批准号: 7209342
• 负责人: GARRETT M ODELL
• 金额: $ 7.02万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7209342
• 关键词: cell adhesion molecules; cell motility; computer data analysis; computer simulation; mathematical model; molecular rearrangement; protein protein interaction

DESCRIPTION (provided by applicant): Cellular machinery is more complex than any technology humans have understood. Comprehending how this machinery self-assembles and works requires synthesizing interactions between molecular parts of cells into functional mechanistic models. Intelligent design of medical interventions requires this. The only tool capable of this synthesis is mathematical models solved on computers. Detailed case studies of particular cell biological phenomena, not abstract rhetoric, will sharpen this tool and prove its worth. The proposed Center of Excellence at Friday Harbor Laboratories will assemble a cross-disciplinary group of 14 scientists plus staff with this mission: to combine experiment and theory with computational modeling techniques the proposers have helped pioneer into detailed case studies of genetic networks operating in two different contexts-developmental pattern formation and cytoskeletal dynamics, and to promulgate this approach, and the tools supporting it. These studies will consolidate and extend the proposers' current efforts to comprehend: 1) how modules of cross-regulatory genes, installed identically in each cell in an embryo, form and stabilize spatio-temporal gene expression patterns causing cell determination; and 2) how biochemical and mechanical interactions among major cytoskeletal filament systems, molecular motors, cell adhesion proteins, and their myriad regulators cause cells to reorganize their internal components, move, change shape, and divide. Recruiting long-term salaried post-does and visiting sabbatical scientists to the Center and collaborating with them to make models of these phenomena, will teach them to wed computational modeling and experiments to comprehend biological complexity. Center outreach activities will include: 1) Perfecting and publishing computational methods for making and analyzing models of regulatory and cytoskeletal networks; 2) "Hardening' and disseminating our software for building and analyzing gene network models, and for segmenting/visualizing 3D cytoskeletal structure from scanning confocal microscope data; 3) Teaching yearly research apprenticeship courses to recruit biology undergraduates early to careers combining theory, experiment and computation; 4) Hosting teaching workshops and round-table symposia to broadcast the Center's computational modeling successes, facilitate cross-breeding exchange with other scientists and recruit potential converts.

描述（由申请人提供）：蜂窝机械比人类所理解的任何技术都要复杂。理解这种机械如何进行自组装和工作需要将细胞分子部分之间的综合相互作用分解为功能机械模型。医疗干预的智能设计需要此。该合成的唯一工具是在计算机上求解的数学模型。特定细胞生物学现象的详细案例研究，而不是抽象的言论，将使该工具更加清晰并证明其价值。 The proposed Center of Excellence at Friday Harbor Laboratories will assemble a cross-disciplinary group of 14 scientists plus staff with this mission: to combine experiment and theory with computational modeling techniques the proposers have helped pioneer into detailed case studies of genetic networks operating in two different contexts-developmental pattern formation and cytoskeletal dynamics, and to promulgate this approach, and the tools supporting it.这些研究将巩固和扩展提议者当前的理解努力：1）交叉调节基因的模块如何在每个细胞中以胚胎形成并稳定时空基因表达模式，从而导致细胞测定； 2）主要细胞骨骼细胞系统，分子电机，细胞粘附蛋白及其无数调节剂之间的生化和机械相互作用如何导致细胞重新组织其内部组件，移动，改变形状和分裂。招募长期受薪后的后，并访问休假科学家到中心，并与他们合作制定这些现象的模型，将教会他们与计算建模和实验结合，以理解生物学复杂性。中心外展活动将包括：1）完善和发布计算方法，用于制定和分析调节和细胞骨架网络模型； 2）“加强'并传播我们的软件，以构建和分析基因网络模型，以及从扫描共凝聚显微镜数据中进行/可视化3D细胞骨架结构； 3）教学年度研究学徒课程，以招募生物学招募生物学本质，以招募早期的计算和计算范围；成功，促进与其他科学家的杂交交流，并招募潜在的convert依。